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Despite intense scrutiny, the signals that determine whether a given RNA is degraded by the highly conserved and selective nonsense‐mediated RNA decay (NMD) pathway remain murky. In this issue of The EMBO Journal, Kishor et al shed light on this issue by demonstrating that the RNA‐binding protein, hnRNP L, protects a subset of RNAs from degradation by NMD. This mechanism is responsible for stabilizing the mRNA encoding the pro‐survival “oncogenic” protein, BCL‐2, in B‐cell lymphoma.

See also: A Kishor et al

The EMBO Journal (2019) e101417

The expression of a gene depends just as much on the stability of the mRNA it encodes as the rate at which it is transcribed. Indeed, regulation of RNA stability confers qualities not offered by transcriptional control, such as the ability to rapidly eliminate an mRNA when its gene product is no longer needed. While much has been learnt about RNA decay mechanisms, we are still largely in the dark as to the specific signals that ultimately determine their activity. There is no better example of this than nonsense‐mediated decay (NMD), a highly selective RNA turnover pathway triggered by stop codons in specific contexts. It has been particularly perplexing why a given context—such as a long 3′ untranslated region (3′UTR) downstream of the stop codon—triggers NMD in some RNAs but not others. In this issue of The EMBO Journal, Kishor et al significantly fill this gap by defining a key molecule that determines whether or not a long 3′UTR elicits RNA decay (Kishor et al, 2019).

NMD was originally discovered through its role as a quality control mechanism that degrades aberrant mRNAs harboring premature termination codons generated by mutations, errors in splicing, and programmed gene rearrangements (Fig 1A; Nickless et al, 2017). Subsequently, NMD was found to …

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